The trigger for malignant hyperthermia. What makes this the clearest case in pharmacogenomics is that the alternative is easy: an anaesthetic without any of these agents is routine, provided somebody knows beforehand.
Avoid in a person with a susceptible genotype. These agents open the ryanodine receptor and are the classic trigger for a malignant hyperthermia crisis. A trigger-free anaesthetic is straightforward to plan when the anaesthetist knows in advance, which is the entire clinical value of this information.
CPIC Guideline for CACNA1S, RYR1 and Volatile Anesthetic Agents and Succinylcholine (Clin Pharmacol Ther 2019, PMID 30499100).
Avoid in a person with a susceptible genotype. Succinylcholine triggers the same crisis and can also cause masseter spasm. Non-depolarising neuromuscular blockers are the alternative.
CPIC Guideline for CACNA1S, RYR1 and Volatile Anesthetic Agents and Succinylcholine (Clin Pharmacol Ther 2019, PMID 30499100).
CACNA1S encodes the voltage sensor that tells RYR1 to release calcium, and variants in it cause the same susceptibility through the same pathway. It accounts for a smaller share of cases than RYR1, and the prescribing consequence is identical: avoid the triggering agents.
CPIC Guideline for CACNA1S, RYR1 and Volatile Anesthetic Agents and Succinylcholine (Clin Pharmacol Ther 2019, PMID 30499100).
Every guideline above was written by people. Named here because they are contributors to this page in the same sense anybody else on this site is.
These are the positions in your own file that carry the genes above. Not every gene in a guideline is one we report — where that is the case the gene appears above without a variant here, and the note says so.
CACNA1S · rs3850625
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